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Introduction The coronavirus disease 2019 (COVID-19) pandemic continues to be a global threat, with tremendous resources invested into identifying risk factors for severe COVID-19 illness. The objective of this study was to analyze the characteristics and outcomes of male compared to female adults with COVID-19 who required hospitalization within US academic centers. Methods Using the Vizient clinical database, discharge records of adults with a diagnosis of COVID-19 between March 1, 2020 and November 30, 2020 were reviewed. Outcome measures included demographics, characteristics, length of hospital stay, rate of respiratory intubation and mechanical ventilation, and rate of in-hospital mortality of male vs female according to age, race/ethnicity, and presence of preexisting comorbidities. Results Among adults with COVID-19, 161,206 were male while 146,804 were female. Adult males with COVID-19 were more likely to have hypertension (62.1% vs 59.6%, p Conclusion This large analysis of 308,010 COVID-19 adults hospitalized at US academic centers showed that males have a higher rate of respiratory intubation and longer length of hospital stay compared to females and have a higher death rate even when compared across age groups, race/ethnicity, payers, and comorbidity.

Background Acute kidney injury (AKI) is increasingly encountered in community settings and contributes to morbidity, mortality, and increased resource utilization worldwide. In low-resource settings, lack of awareness of and limited access to diagnostic and therapeutic interventions likely influence patient management. We evaluated the feasibility of the use of point-of-care (POC) serum creatinine and urine dipstick testing with an education and training program to optimize the identification and management of AKI in the community in 3 low-resource countries. Methods and findings Patients presenting to healthcare centers (HCCs) from 1 October 2016 to 29 September 2017 in the cities Cochabamba, Bolivia; Dharan, Nepal; and Blantyre, Malawi, were assessed utilizing a symptom-based risk score to identify patients at moderate to high AKI risk. POC testing for serum creatinine and urine dipstick at enrollment were utilized to classify these patients as having chronic kidney disease (CKD), acute kidney disease (AKD), or no kidney disease (NKD). Patients were followed for a maximum of 6 months with repeat POC testing. AKI development was assessed at 7 days, kidney recovery at 1 month, and progression to CKD and mortality at 3 and 6 months. Following an observation phase to establish baseline data, care providers and physicians in the HCCs were trained with a standardized protocol utilizing POC tests to evaluate and manage patients, guided by physicians in referral hospitals connected via mobile digital technology. We evaluated 3,577 patients, and 2,101 were enrolled: 978 in the observation phase and 1,123 in the intervention phase. Due to the high number of patients attending the centers daily, it was not feasible to screen all patients to assess the actual incidence of AKI. Of enrolled patients, 1,825/2,101 (87%) were adults, 1,117/2,101 (53%) were females, 399/2,101 (19%) were from Bolivia, 813/2,101 (39%) were from Malawi, and 889/2,101 (42%) were from Nepal. The age of enrolled patients ranged from 1 month to 96 years, with a mean of 43 years (SD 21) and a median of 43 years (IQR 27–62). Hypertension was the most common comorbidity (418/2,101; 20%). At enrollment, 197/2,101 (9.4%) had CKD, and 1,199/2,101 (57%) had AKD. AKI developed in 30% within 7 days. By 1 month, 268/978 (27%) patients in the observation phase and 203/1,123 (18%) in the intervention phase were lost to follow-up. In the intervention phase, more patients received fluids (observation 714/978 [73%] versus intervention 874/1,123 [78%]; 95% CI 0.63, 0.94; p = 0.012), hospitalization was reduced (observation 578/978 [59%] versus intervention 548/1,123 [49%]; 95% CI 0.55, 0.79; p < 0.001), and admitted patients with severe AKI did not show a significantly lower mortality during follow-up (observation 27/135 [20%] versus intervention 21/178 [11.8%]; 95% CI 0.98, 3.52; p = 0.057). Of 504 patients with kidney function assessed during the 6-month follow-up, de novo CKD arose in 79/484 (16.3%), with no difference between the observation and intervention phase (95% CI 0.91, 2.47; p = 0.101). Overall mortality was 273/2,101 (13%) and was highest in those who had CKD (24/106; 23%), followed by those with AKD (128/760; 17%), AKI (85/628; 14%), and NKD (36/607; 6%). The main limitation of our study was the inability to determine the actual incidence of kidney dysfunction in the health centers as it was not feasible to screen all the patients due to the high numbers seen daily. Conclusions This multicenter, non-randomized feasibility study in low-resource settings demonstrates that it is feasible to implement a comprehensive program utilizing POC testing and protocol-based management to improve the recognition and management of AKI and AKD in high-risk patients in primary care., Etienne Macedo and colleagues report on a point-of-care testing program for acute kidney injury and disease in high-risk primary care patients., Author summary Why was this study done? The study was designed to assess the feasibility of implementing interventions to optimize care of acute kidney injury (AKI). We used a comprehensive 5R approach—risk, recognition, response, renal support, and rehabilitation—to test the intervention in resource-constrained regions in Africa, Asia, and Latin America. What did the researchers do and find? Patients seen in community healthcare centers were screened and assigned a risk level for AKI based on their presenting signs and symptoms. Patients with moderate to high risk were approached for consent and enrolled in the study, underwent kidney function assessment, and were followed for their disposition and outcomes. Kidney function was assessed using point-of-care (POC) tests that included a test strip for measuring creatinine level in the blood using a portable device and a urine dipstick test to evaluate for proteinuria. What do these findings mean? The ISN 0by25 trial successfully demonstrated the utility of a symptom-based health assessment risk score coupled with a POC creatinine and urine dipstick test in early recognition of kidney disease and appropriate triaging and management of patients presenting to primary healthcare centers in low-income countries. Kidney dysfunction was associated with an increased risk of mortality, which was higher in patients with a moderate severity of AKI. Recognition and management of patients was facilitated by the combination of the POC test and guidance through teleconsultation.

According to the efficient coding hypothesis, sensory systems are adapted to maximize their ability to encode information about the environment. Sensory neurons play a key role in encoding by selectively modulating their firing rate for a subset of all possible stimuli. This pattern of modulation is often summarized via a tuning curve. The optimally efficient distribution of tuning curves has been calculated in variety of ways for one-dimensional (1-D) stimuli. However, many sensory neurons encode multiple stimulus dimensions simultaneously. It remains unclear how applicable existing models of 1-D tuning curves are for neurons tuned across multiple dimensions. We describe a mathematical generalization that builds on prior work in 1-D to predict optimally efficient multidimensional tuning curves. Our results have implications for interpreting observed properties of neuronal populations. For example, our results suggest that not all tuning curve attributes (such as gain and bandwidth) are equally useful for evaluating the encoding efficiency of a population., Author summary Our brains are tasked with processing a wide range of sensory inputs from the world around us. Natural sensory inputs are often complex and composed of multiple distinctive features (for example, an object may be characterized by its size, shape, color, and weight). Many neurons in the brain play a role in encoding multiple features, or dimensions, of sensory stimuli. Here, we employ the computational technique of population modeling to examine how groups of neurons in the brain can optimally encode multiple dimensions of sensory stimuli. This work provides predictions for theory-driven experiments that can leverage emerging high-throughput neural recording tools to characterize the properties of neuronal populations in response to complex natural stimuli.

The spread of Aedes aegypti in California and other regions of the U.S. has increased the need to understand the potential for local chains of Ae. aegypti-borne virus transmission, particularly in arid regions where the ecology of these mosquitoes is less understood. For public health and vector control programs, it is helpful to know whether variation in risk of local transmission can be attributed to socio-demographic factors that could help to target surveillance and control programs. Socio-demographic factors have been shown to influence transmission risk of dengue virus outside the U.S. by modifying biting rates and vector abundance. In regions of the U.S. where Ae. aegypti have recently invaded and where residential areas are structured differently than those in the tropics where Ae. aegypti are endemic, it is unclear how socio-demographic factors modify the abundance of Ae. aegypti populations. Understanding heterogeneities among households in Ae. aegypti abundance will provide a better understanding of local vectorial capacity and is an important component of understanding risk of local Ae. aegypti-borne virus transmission. We conducted a cross-sectional study in Los Angeles County, California during summer 2017 to understand the causes of variation in relative abundance of Ae. aegypti among households. We surveyed 161 houses, representing a wide range of incomes. Surveys consisted of systematic adult mosquito collections, inspections of households and properties, and administration of a questionnaire in English or Spanish. Adult Ae. aegypti were detected at 72% of households overall and were found indoors at 12% of households. An average of 3.1 Ae. aegypti were collected per household. Ae. aegypti abundance outdoors was higher in lower-income neighborhoods and around older households with larger outdoor areas, greater densities of containers with standing water, less frequent yard maintenance, and greater air-conditioner use. We also found that Ae. aegypti abundance indoors was higher in households that had less window and door screening, less air-conditioner usage, more potted plants indoors, more rain-exposed containers around the home, and lower neighborhood human population densities. Our results indicate that, in the areas of southern California studied, there are behavioral and socio-demographic determinants of Ae. aegypti abundance, and that low-income households could be at higher risk for exposure to Ae. aegypti biting and potentially greater risk for Zika, dengue, and chikungunya virus transmission if a local outbreak were to occur., Author summary Understanding the factors that influence the spread and population growth of Aedes aegypti, the primary mosquito vector of Zika, dengue, and chikungunya viruses, will aid vector control and public health agencies to identify the communities most at risk for Ae. aegypti biting. This study found associations between increased Ae. aegypti abundance and mappable socioeconomic variables that can serve as a basis for targeted control strategies. We describe neighborhood- and household-scale risk factors associated with increased Ae. aegypti abundance in Los Angeles, California, an area that historically has had a relatively high number of travelers return home that are infected with Zika and dengue viruses. Our results show that Ae. aegypti is more abundant in lower income communities in Los Angeles and that several household, behavioral, and socio-demographic characteristics are associated with increased abundance of Ae. aegypti. Our findings have the potential to help vector control agencies identify communities at risk of increased household Ae. aegypti abundance and develop community-specific interventions to minimize household infestations.

INTRODUCTION:As facility-based deliveries increase globally, maternity registers offer a promising way of documenting pregnancy outcomes and understanding opportunities for perinatal mortality prevention. This study aims to contribute to global quality improvement efforts by characterizing facility-based pregnancy outcomes in Kenya and Uganda including maternal, neonatal, and fetal outcomes at the time of delivery and neonatal discharge outcomes using strengthened maternity registers. METHODS:Cross sectional data were collected from strengthened maternity registers at 23 facilities over 18 months. Data strengthening efforts included provision of supplies, training on standard indicator definitions, and monthly feedback on completeness. Pregnancy outcomes were classified as live births, early stillbirths, late stillbirths, or spontaneous abortions according to birth weight or gestational age. Discharge outcomes were assessed for all live births. Outcomes were assessed by country and by infant, maternal, and facility characteristics. Maternal mortality was also examined. RESULTS:Among 50,981 deliveries, 91.3% were live born and, of those, 1.6% died before discharge. An additional 0.5% of deliveries were early stillbirths, 3.6% late stillbirths, and 4.7% spontaneous abortions. There were 64 documented maternal deaths (0.1%). Preterm and low birthweight infants represented a disproportionate number of stillbirths and pre-discharge deaths, yet very few were born at ≤1500g or

Author(s): Phan, Binh An P; Ma, Yifei; Scherzer, Rebecca; Deeks, Steven G; Hsue, Priscilla Y | Abstract: BackgroundWhile HIV infection is associated with increased cardiovascular risk, benefit from statin is not well established in HIV-infected adults. We assessed whether statins are associated with a decrease in carotid artery intima-media thickness (cIMT) progression and all-cause mortality in HIV-infected adults who are at elevated ASCVD risk and recommended for statins.MethodsCarotid IMT was measured at baseline and follow-up in 127 HIV-infected adults who meet ACC/AHA criteria to be on statins. Inverse probability of treatment weighting (IPTW) was used to address selection bias. Multivariable models were used to control for baseline characteristics.Results28 subjects (22%) were on statins and 99 subjects (78%) were not. Mean cIMT at baseline was 1.2 mm (SD = 0.34) in statin users and 1.1 mm (SD = 0.34) in non-users, and the multivariable adjusted difference was 0.05mm (95%CI -0.11, 0.21 p = 0.53). After 3.2 years of follow-up, average cIMT progression was similar in statin users and non-users (0.062mm/yr vs. 0.058 mm/yr) and the multivariable adjusted difference over the study period was 0.004 mm/yr (95% CI -0.018, 0.025, p = 0.74). All-cause mortality appeared higher in non-statin users compared with statin users, but the difference was not significant (adjusted HR = 0.74, 95%CI 0.17-3.29, p = 0.70).ConclusionIn a HIV cohort who had elevated ASCVD risk and meet ACC/AHA criteria for statins, treatment with statins was not associated with a reduction in carotid atherosclerosis progression or total mortality. Future studies are needed to further explore the impact of statins on cardiovascular risk in the HIV-infected population.

An outbreak of Rocky Mountain spotted fever (RMSF) transmitted by the brown dog tick (Rhipicephalus sanguineus sensu lato) has emerged as a major human and animal health concern in Mexicali, Mexico. Due to high rates of brown dog tick infestation, susceptibility, and association with humans, dogs serve as sentinels and have a key role in the ecology of RMSF. A cross-sectional household questionnaire study was conducted in six rural and urban locations to characterize dog ecology and demography in RMSF high-and low-risk areas of Mexicali. In addition, we tracked movement patterns of 16 dogs using a GPS data logger. Of 253 households, 73% owned dogs, and dog ownership tended to be higher in high-risk areas, with a mean dog:human ratio of 0.43, compared with 0.3 in low-risk areas. Dogs in high-risk areas had higher fecundity and roamed more, but the dog density and numbers of free-roaming dogs were comparable. There was a higher proportion of younger dogs and lower proportion of older dogs in high-risk areas. The high proportion of immunologically naïve puppies in high risk areas could result in a lack of herd immunity leading to a more vulnerable dog and human population. The marked increase of space use of free-roaming dogs in high-risk areas suggests that unrestrained dogs could play an important role in spreading ticks and pathogens. As means to limit RMSF risk, practical changes could include increased efforts for spay-neuter and policies encouraging dog restraint to limit canine roaming and spread of ticks across communities; due to dog density is less impactful such policies may be more useful than restrictions on the number of owned dogs.

Life history theory examines how characteristics of organisms, such as age and size at maturity, may vary through natural selection as evolutionary responses that optimize fitness. Here we ask how predictions of age and size at maturity differ for the three classical fitness functions-intrinsic rate of natural increase r, net reproductive rate R0, and reproductive value Vx-for semelparous species. We show that different choices of fitness functions can lead to very different predictions of species behavior. In one's efforts to understand an organism's behavior and to develop effective conservation and management policies, the choice of fitness function matters. The central ingredient of our approach is the maturation reaction norm (MRN), which describes how optimal age and size at maturation vary with growth rate or mortality rate. We develop a practical geometric construction of MRNs that allows us to include different growth functions (linear growth and nonlinear von Bertalanffy growth in length) and develop two-dimensional MRNs useful for quantifying growth-mortality trade-offs. We relate our approach to Beverton-Holt life history invariants and to the Stearns-Koella categorization of MRNs. We conclude with a detailed discussion of life history parameters for Great Lakes Chinook Salmon and demonstrate that age and size at maturity are consistent with predictions using R0 (but not r or Vx) as the underlying fitness function.

Mount Everest is an extreme environment for humans. Nevertheless, hundreds of mountaineers attempt to summit Everest each year. In a previous study we analyzed interview data for all climbers (2,211) making their first attempt on Everest during 1990-2005. Probabilities of summiting were similar for men and women, declined progressively for climbers about 40 and older, but were elevated for climbers with experience climbing in Nepal. Probabilities of dying were also similar for men and women, increased for climbers about 60 and older (especially for the few that had summited), and were independent of experience. Since 2005, many more climbers (3,620) have attempted Everest. Here our primary goal is to quantify recent patterns of success and death and to evaluate changes over time. Also, we investigate whether patterns relate to key socio-demographic covariates (age, sex, host country, prior experience). Recent climbers were more diverse both in gender (women = 14.6% vs. 9.1% for 1990-2005) and in age (climbers ≥ 40 = 54.1% vs. 38.7%). Strikingly, recent climbers of both sexes were almost twice as likely to summit-and slightly less likely to die-than were comparable climbers in the previous survey. Temporal shifts may reflect improved weather forecasting, installation of fixed ropes on much of the route, and accumulative logistic equipment and experience. We add two new analyses. The probability of dying from illness or non-traumas (e.g., high-altitude illness, hypothermia), relative to dying from falling or from 'objective hazards' (avalanche, rock or ice fall), increased marginally with age. Recent crowding during summit bids was four-fold greater than in the prior sample, but surprisingly crowding has no evident effect on success or death during summit bids. Our results inform prospective climbers as to their current odds of success and of death, as well as inform governments of Nepal and China of the safety consequences and economic impacts of periodically debated restrictions based on climber age and experience.

Understanding the coagulation process is critical to developing treatments for trauma and coagulopathies. Clinical studies on tranexamic acid (TXA) have resulted in mixed reports on its efficacy in improving outcomes in trauma patients. The largest study, CRASH-2, reported that TXA improved outcomes in patients who received treatment prior to 3 hours after the injury, but worsened outcomes in patients who received treatment after 3 hours. No consensus has been reached about the mechanism behind the duality of these results. In this paper we use a computational model for coagulation and fibrinolysis to propose that deficiencies or depletions of key anti-fibrinolytic proteins, specifically antiplasmin, a1-antitrypsin and a2-macroglobulin, can lead to worsened outcomes through urokinase-mediated hyperfibrinolysis.

Background Injection drug use (IDU) is associated with multiple health harms. The vast majority of IDU initiation events (in which injection-naïve persons first adopt IDU) are assisted by a person who injects drugs (PWID), and as such, IDU could be considered as a dynamic behavioral transmission process. Data suggest that opioid agonist treatment (OAT) enrollment is associated with a reduced likelihood of assisting with IDU initiation. We assessed the association between recent OAT enrollment and assisting IDU initiation across several North American settings and used dynamic modeling to project the potential population-level impact of OAT scale-up within the PWID population on IDU initiation. Methods and findings We employed data from a prospective multicohort study of PWID in 3 settings (Vancouver, Canada [n = 1,737]; San Diego, United States [n = 346]; and Tijuana, Mexico [n = 532]) from 2014 to 2017. Site-specific modified Poisson regression models were constructed to assess the association between recent (past 6 month) OAT enrollment and history of ever having assisted an IDU initiation with recently assisting IDU initiation. Findings were then pooled using linear mixed-effects techniques. A dynamic transmission model of IDU among the general population was developed, stratified by known factors associated with assisting IDU initiation and relevant drug use behaviors. The model was parameterized to a generic North American setting (approximately 1% PWID) and used to estimate the impact of increasing OAT coverage among PWID from baseline (approximately 21%) to 40%, 50%, and 60% on annual IDU initiation incidence and corresponding PWID population size across a decade. From Vancouver, San Diego, and Tijuana, respectively, 4.5%, 5.2%, and 4.3% of participants reported recently assisting an IDU initiation, and 49.4%, 19.7%, and 2.1% reported recent enrollment in OAT. Recent OAT enrollment was significantly associated with a 45% lower likelihood of providing recent IDU initiation assistance among PWID (relative risk [RR] 0.55 [95% CI 0.36–0.84], p = 0.006) compared to those not recently on OAT. Our dynamic model predicts a baseline mean of 1,067 (2.5%–97.5% interval [95% I 490–2,082]) annual IDU initiations per 1,000,000 individuals, of which 886 (95% I 406–1,750) are assisted by PWID. Based on our observed statistical associations, our dynamic model predicts that increasing OAT coverage from approximately 21% to 40%, 50%, or 60% among PWID could reduce annual IDU initiations by 11.5% (95% I 2.4–21.7), 17.3% (95% I 5.6–29.4), and 22.8% (95% I 8.1–36.8) and reduce the PWID population size by 5.4% (95% I 0.1–12.0), 8.2% (95% I 2.2–16.9), and 10.9% (95% I 3.2–21.8) relative to baseline, respectively, in a decade. Less impact occurs when the protective effect of OAT is diminished, when a greater proportion of IDU initiations are unassisted by PWID, and when average IDU career length is longer. The study’s main limitations are uncertainty in the causal pathway between OAT enrollment and assisting with IDU initiation and the use of a simplified model of IDU initiation. Conclusions In addition to its known benefits on preventing HIV, hepatitis C virus (HCV), and overdose among PWID, our modeling suggests that OAT scale-up may also reduce the number of IDU initiations and PWID population size., In a modelling study, Natasha Martin and co-workers estimate the impact of increased use of opioid agonist therapy on initiation of injection drug use., Author summary Why was this study done? The majority of injection drug use (IDU) initiations are assisted by people who inject drugs (PWID). Evidence from North America indicates that PWID receiving opioid agonist treatment (OAT; such as methadone or buprenorphine) are less likely to have provided assistance with IDU initiation. We used dynamic modeling to assess the impact of scaling up OAT coverage among PWID on IDU initiations in the next decade in a generic North American setting. What did the researchers do and find? We used cohort data among PWID from Vancouver, Canada; San Diego, United States; and Tijuana, Mexico, to assess the relationship between recent OAT enrollment and recent provision of assistance with IDU initiation, finding that past–6-month enrollment in OAT was associated with nearly half the likelihood of past–6-month provision of assistance with IDU initiation. Using these associations, we parameterized a dynamic model of IDU initiation and assessed the population-level impact of scaling up OAT coverage on IDU initiations over the next decade in a generic North American setting. We estimate that if OAT coverage is scaled up from approximately 21% to 60% among PWID, the number of people who initiate IDU each year will decrease by 23% after a decade. What do these findings mean? In addition to its known benefits of preventing HIV, hepatitis C virus (HCV), and overdose among PWID, our findings suggest that increasing OAT coverage among PWID can have an important impact on reducing IDU initiations.

Background Socioeconomic disparities in infant mortality have persisted for decades in high-income countries and may have become stronger in some populations. Therefore, new understandings of the mechanisms that underlie socioeconomic differences in infant deaths are essential for creating and implementing health initiatives to reduce these deaths. We aimed to explore whether and the extent to which preterm birth (PTB) and small for gestational age (SGA) at birth mediate the association between maternal education and infant mortality. Methods and findings We developed a population-based cohort study to include all 1,994,618 live singletons born in Denmark in 1981–2015. Infants were followed from birth until death, emigration, or the day before the first birthday, whichever came first. Maternal education at childbirth was categorized as low, medium, or high. An inverse probability weighting of marginal structural models was used to estimate the controlled direct effect (CDE) of maternal education on offspring infant mortality, further split into neonatal (0–27 days) and postneonatal (28–364 days) deaths, and portion eliminated (PE) by eliminating mediation by PTB and SGA. The proportion eliminated by eliminating mediation by PTB and SGA was reported if the mortality rate ratios (MRRs) of CDE and PE were in the same direction. The MRRs between maternal education and infant mortality were 1.63 (95% CI 1.48–1.80, P < 0.001) and 1.19 (95% CI 1.08–1.31, P < 0.001) for low and medium versus high education, respectively. The estimated proportions of these total associations eliminated by reducing PTB and SGA together were 55% (MRRPE = 1.27, 95% CI 1.15–1.40, P < 0.001) for low and 60% (MRRPE = 1.11, 95% CI 1.01–1.22, P = 0.037) for medium versus high education. The proportions eliminated by eliminating PTB and SGA separately were, respectively, 46% and 11% for low education (versus high education) and 48% and 13% for medium education (versus high education). PTB and SGA together contributed more to the association of maternal educational disparities with neonatal mortality (proportion eliminated: 75%–81%) than with postneonatal mortality (proportion eliminated: 21%–23%). Limitations of the study include the untestable assumption of no unmeasured confounders for the causal mediation analysis, and the limited generalizability of the findings to other countries with varying disparities in access and quality of perinatal healthcare. Conclusions PTB and SGA may play substantial roles in the relationship between low maternal education and infant mortality, especially for neonatal mortality. The mediating role of PTB appeared to be much stronger than that of SGA. Public health strategies aimed at reducing neonatal mortality in high-income countries may need to address socially related prenatal risk factors of PTB and impaired fetal growth. The substantial association of maternal education with postneonatal mortality not accounted for by PTB or SGA could reflect unaddressed educational disparities in infant care or other factors., Bo Fu and colleagues analyse factors that may mediate associations between maternal education and child health., Author summary Why was this study done? Infant mortality in high-income countries has decreased in recent decades. However, socioeconomic inequality in infant mortality remains and may have become stronger in some populations. This study provides in-depth knowledge on the underlying pathways from maternal socioeconomic inequality to infant mortality, which is important for developing preventive strategies to reduce potentially preventable deaths. What did the researchers do and find? We conducted a national population-based cohort study that included all 1.99 million live singletons born in Denmark in 1981–2015. Using modern modeling methods for causal mediation analysis, we found that preterm birth and restricted fetal growth may mediate the association between low maternal education and infant mortality. The mediated effects through preterm birth and restricted fetal growth were substantial for neonatal mortality but not for postneonatal mortality. The effect through preterm birth seemed to be greater than that through restricted fetal growth. What do these findings mean? Public health strategies could aim to reduce educational differences in the death of newborns in high-income countries by addressing socially related risk factors for preterm birth and impaired fetal growth, such as the accessibility and quality of maternity and perinatal care, or maternal lifestyle factors. The substantial direct impact of low maternal education on postneonatal death not explained by preterm birth or restricted fetal growth could be due to unaddressed educational inequality in infant care or other factors such as housing conditions, the quality of medical care, or the use of specialized medical care.

Author(s): Dolan, Carrie B; BenYishay, Ariel; Grepin, Karen A; Tanner, Jeffery C; Kimmel, April D; Wheeler, David C; McCord, Gordon C | Abstract: ObjectiveTo test the impact of a nationwide Long-Lasting Insecticidal Nets [LLINs] distribution program in the Democratic Republic of Congo [DRC] on all-cause under-five child mortality exploiting subnational variation in malaria endemicity and the timing in the scale-up of the program across provinces.DesignGeospatial Impact Evaluation using a difference-in-differences approach.SettingDemocratic Republic of the Congo.Participants52,656 children sampled in the 2007 and 2013/2014 DRC Demographic and Health Surveys.InterventionsThe analysis provides plausibly causal estimates of both average treatment effects of the LLIN distribution campaign and geospatial heterogeneity in these effects based on malaria endemicity. It compares the under-five, all-cause mortality for children pre- and post-LLIN campaign relative to children in those areas that had not yet been exposed to the campaign using a difference-in-differences model and controlling for year- and province-fixed effects, and province-level trends in mortality.ResultsWe find that the campaign led to a 41% decline [3.7 percentage points, 95% CI 1.3 to 6.0] in under-5 mortality risk among children living in rural areas with malaria ecology above the sample median. Results were robust to controlling for household assets and the presence of other health aid programs. No effect was detected in children living in areas with malaria ecology below the median.ConclusionThe findings of this paper make important contributions to the evidence base for the effectiveness of large scale-national LLIN campaigns against malaria. We found that the program was effective in areas of the DRC with the highest underlying risk of malaria. Targeting bednets to areas with greatest underlying risk for malaria may help to increase the efficiency of increasingly limited malaria resources but should be balanced against other malaria control concerns.

Using a well-established model species for demographic, behavioural and aging research, the Mediterranean fruit fly (Ceratitis capitata), we explored whether nutritional stress early in adult life affects the sexual performance and survival in older ages. To do so we established two different protein starvation (PS) protocols that included the elimination of proteinaceous diet either before or after sexual maturity of male medflies. The frequency of sexual signalling and the age of death were daily recorded. Sexual signalling is directly related with male mating success in this model system. PS early in adult life results in high mortality rates (similar to sugar-only fed males), which are gradually restored in more advanced ages. Provision of a proteinaceous diet following early-life PS increases straightaway male sexual signalling to levels similar with those having continuous access to proteinaceous diet. Switching diet regimes from a protein-free to a protein-rich one progressively compensates mortality rates. Apparently, males prioritize sexual signalling over lifespan. PS after attaining sexual maturity significantly reduces both longevity and sexual performance. Access to protein only early in life is insufficient to support lifetime energy-consuming behaviours such as sexual signalling. Continuous access to a proteinaceous diet determines both lifetime sexual performance and longevity. Early in life PS males prioritize the allocation of nutritional elements, when available, in sexual activities over soma-maintenance.

Acute respiratory distress syndrome (ARDS) has high rates of mortality and multisystem morbidity. Pre-clinical data suggest that fibroblast growth factor 23 (FGF23) may contribute to pulmonary pathology, and FGF23 is associated with mortality and morbidity, including acute kidney injury (AKI), in non-ARDS cohorts. Here, we assess whether FGF23 is associated with AKI and/or mortality in a cohort of 161 pediatric ARDS patients. Plasma total (intact + C-terminal) FGF23 and intact FGF23 concentrations were measured within 24 hours of ARDS diagnosis (Day 1), and associations with Day 3 AKI and 60-day mortality were evaluated. 35 patients (22%) developed AKI by 3 days post-ARDS diagnosis, and 25 (16%) died by 60 days post-ARDS diagnosis. In unadjusted models, higher Day 1 total FGF23 was associated with Day 3 AKI (odds ratio (OR) 2.22 [95% confidence interval (CI) 1.62, 3.03], p

Excessive alcohol consumption contributes significantly to premature mortality, injuries and morbidity, and a range of U.S. state policies have been shown to reduce these behaviors. Monitoring state alcohol policy environments is essential, but methodologically challenging given that new laws may be passed (or repealed) each year, resulting in considerable variation across states. Existing measures have not been made public or have only a single year available. We develop a new replicable measure, the state alcohol policy score, for each state and year 2004-2009, that captures the essential features of a state's evidence-based alcohol policies. We evaluate its similarity to two existing alcohol policy measures and validate it by replicating findings from a previous study that used one of those measures to assess its relationship with several binge drinking outcomes. Estimates of the association between one-year lagged state alcohol policy scores and state binge drinking outcomes, obtained from the 2005-2010 Behavioral Risk Factor Surveillance System surveys (n = 440,951, 2010), were produced using Generalized Linear Models that controlled for state and individual-level co-variates, with fixed effects for year and region. We find a 10-percentage point increase in the state alcohol policy score was associated with a 9% lower odds of binge drinking (aOR = 0.91, 95% CI 0.89, 0.92; N = 1,992,086), a result consistent for men, women and for most age and race subgroups. We find that gender gaps in binge drinking behaviors narrowed in states with higher state alcohol policy scores. These results were nearly identical to those found in other studies using different scores obtained with the aid of expert opinions. We conclude that the score developed here is a valid measure that can be readily updated for monitoring and evaluating the variation and impact of state alcohol policies and make available our state scores for the years of the study.

In experimental cultures, when bacteria are mixed with lytic (virulent) bacteriophage, bacterial cells resistant to the phage commonly emerge and become the dominant population of bacteria. Following the ascent of resistant mutants, the densities of bacteria in these simple communities become limited by resources rather than the phage. Despite the evolution of resistant hosts, upon which the phage cannot replicate, the lytic phage population is most commonly maintained in an apparently stable state with the resistant bacteria. Several mechanisms have been put forward to account for this result. Here we report the results of population dynamic/evolution experiments with a virulent mutant of phage Lambda, λVIR, and Escherichia coli in serial transfer cultures. We show that, following the ascent of λVIR-resistant bacteria, λVIR is maintained in the majority of cases in maltose-limited minimal media and in all cases in nutrient-rich broth. Using mathematical models and experiments, we show that the dominant mechanism responsible for maintenance of λVIR in these resource-limited populations dominated by resistant E. coli is a high rate of either phenotypic or genetic transition from resistance to susceptibility—a hitherto undemonstrated mechanism we term "leaky resistance." We discuss the implications of leaky resistance to our understanding of the conditions for the maintenance of phage in populations of bacteria—their “existence conditions.”, Author summary While it is clear that bacteriophage abound in bacterial communities, their role in the ecology and evolution of these communities remains poorly understood. Fundamental questions remain unanswered, such as, are phage regulating the population densities of their host bacteria? And how are virulent phage maintained in bacterial communities, following the seemingly inevitable evolution of resistant bacteria? Here we present a theoretical and experimental investigation to provide evidence for a new mechanism for maintaining phage in populations dominated by resistant bacteria. This mechanism, which we term “leaky resistance,” is based on a high rate of either phenotypic or genetic transition from resistance to susceptibility.

Author(s): Litwinowicz, Radoslaw; Bartus, Magdalena; Burysz, Marian; Brzezinski, Maciej; Suwalski, Piotr; Kapelak, Boguslaw; Vuddanda, Venkat; Lakkireddy, Dhanunjaya; Lee, Randall J; Trabka, Rafal; Bartus, Krzysztof | Abstract: INTRODUCTION:Left atrial appendage closure (LAAC) with LARIAT offers an alternative to oral anticoagulation (OAC) for patients with atrial fibrillation. The aim of this study was to present long-term clinical outcomes of LAAC in these patients (AF). MATERIAL AND METHODS:A prospective, single-center study was performed in 139 patients undergoing LAAC with Lariat. Thromboembolic events, severe bleeding and mortality rate were recorded. The reduction in risk of thromboembolism and bleeding after LAAC was calculated. RESULTS:The mean CHADS2-score was 1.8 ± 1.0, mean CHA2DS2-VASc score was 2.9 ± 1.6 and HAS-BLED score was 3.1 ± 1.1. After 428.4 patient-years of follow-up (mean 4.2±1.0 years), the thromboembolism rate was 0.6% with a calculated thromboembolism risk reduction of 81%. The severe bleeding rate was 0.8%; calculated bleeding risk reduction was 78%. The overall mortality rate was 1.6%. CONCLUSIONS:Long-term outcomes show that LAAC with Lariat is a safe and effective treatment for stroke prevention and bleeding risk reduction in AF patients with a high level of underlying risk.

Background Survival represents the single most important indicator of successful HIV treatment. Routine monitoring fails to capture most deaths. As a result, both regional assessments of the impact of HIV services and identification of hotspots for improvement efforts are limited. We sought to assess true mortality on treatment, characterize the extent under-reporting of mortality in routine health information systems in Zambia, and identify drivers of mortality across sites and over time using a multistage, regionally representative sampling approach. Methods and findings We enumerated all HIV infected adults on antiretroviral therapy (ART) who visited any one of 64 facilities across 4 provinces in Zambia during the 24-month period from 1 August 2013 to 31 July 2015. We identified a probability sample of patients who were lost to follow-up through selecting facilities probability proportional to size and then a simple random sample of lost patients. Outcomes among patients lost to follow-up were incorporated into survival analysis and multivariate regression through probability weights. Of 165,464 individuals (64% female, median age 39 years (IQR 33–46), median CD4 201 cells/mm3 (IQR 111–312), the 2-year cumulative incidence of mortality increased from 1.9% (95% CI 1.7%–2.0%) to a corrected rate of 7.0% (95% CI 5.7%–8.4%) (all ART users) and from 2.1% (95% CI 1.8%–2.4%) to 8.3% (95% CI 6.1%–10.7%) (new ART users). Revised provincial mortality rates ranged from 3–9 times higher than naïve rates for new ART users and were lowest in Lusaka Province (4.6 per 100 person-years) and highest in Western Province (8.7 per 100 person-years) after correction. Corrected mortality rates varied markedly by clinic, with an IQR of 3.5 to 7.5 deaths per 100 person-years and a high of 13.4 deaths per 100 person-years among new ART users, even after adjustment for clinical (e.g., pretherapy CD4) and contextual (e.g., province and clinic size) factors. Mortality rates (all ART users) were highest year 1 after treatment at 4.6/100 person-years (95% CI 3.9–5.5), 2.9/100 person-years (95% CI 2.1–3.9) in year 2, and approximately 1.6% per year through 8 years on treatment. In multivariate analysis, patient-level factors including male sex and pretherapy CD4 levels and WHO stage were associated with higher mortality among new ART users, while male sex and HIV disclosure were associated with mortality among all ART users. In both cases, being late (>14 days late for appointment) or lost (>90 days late for an appointment) was associated with deaths. We were unable to ascertain the vital status of about one-quarter of those lost and selected for tracing and did not adjudicate causes of death. Conclusions HIV treatment in Zambia is not optimally effective. The high and sustained mortality rates and marked under-reporting of mortality at the provincial-level and unexplained heterogeneity between regions and sites suggest opportunities for the use of corrected mortality rates for quality improvement. A regionally representative sampling-based approach can bring gaps and opportunities for programs into clear epidemiological focus for local and global decision makers., To improve estimates of mortality for patients who initiate HIV treatment, Charles Holmes and colleagues use a multistage sampling approach to find and trace health outcomes for patients lost to follow-up after starting antiretroviral therapy in Zambia., Author summary Why was this study done? Previous studies from cohorts in South Africa and parts of East Africa have suggested that site-level reporting of mortality is incomplete. We wanted to understand the degree to which this phenomenon was impacting HIV outcomes at a broader scale, in this case at the provincial level in Zambia, a country with one of the highest burdens of HIV. We also wanted to gain an in-depth understanding of differences between the outcomes of clinical care sites in order to assess the role of mortality as a potential quality improvement target. What did the researchers do and find? From a source population of patients in 4 provinces (Lusaka, Southern, Eastern, and Western) who visited government-operated HIV treatment sites in these provinces, we conducted a multistage sampling approach of a stratified selection of sites and a random sample of patients lost to follow-up. Lost patients were traced and their vital status was ascertained, which was used to enable a corrected regionally representative estimate of survival after starting antiretroviral therapy (ART) as well as corrected site-specific mortality estimates. Of 165,464 individuals, the 2-year cumulative incidence of mortality increased from 1.9% to 7.0% for all ART users and from 2.1% to 8.3% for new ART users, and provincial-level mortality rates rose 3- to 8-fold once corrected for true outcomes. Being late (>14 days late for appointment) or lost (>90 days late for an appointment) was associated with death. What do these findings mean? Deaths are under-reported within the Zambian HIV program, and mortality rates are highly variable across sites and provinces. Our findings enable national- and global-level policy makers to correct existing underestimates of mortality, link these data to quality improvement efforts, and reprioritize interventions to target regional and site-level reductions in mortality as a goal of HIV programs. We have also established that this methodology is feasible for use as a representative surveillance tool for accurate monitoring of provincial and potentially national levels of mortality, even as vital status registries and data systems are further developed and strengthened.

Author(s): Cho, Yun-Kyeong; Nam, Chang-Wook; Koo, Bon-Kwon; Schulman-Marcus, Joshua; Hartaigh, Briain O; Gransar, Heidi; Lu, Yao; Achenbach, Stephan; Al-Mallah, Mouaz; Andreini, Daniele; Bax, Jeroen J; Budoff, Matthew J; Cademartiri, Filippo; Callister, Tracy Q; Chang, Hyuk-Jae; Chinnaiyan, Kavitha; Chow, Benjamin JW; Cury, Ricardo C; Delago, Augustin; Feuchtner, Gudrun; Hadamitzky, Martin; Hausleiter, Jorg; Kaufmann, Philipp A; Kim, Yong-Jin; Leipsic, Jonathon; Maffei, Erica; Marques, Hugo; Pontone, Gianluca; Raff, Gilbert L; Rubinshtein, Ronen; Shaw, Leslee J; Villines, Todd C; Berman, Daniel S; Jones, Erica C; Pena, Jessica M; Lin, Fay Y; Min, James K | Abstract: BackgroundThe extent to which the presence and extent of subclinical atherosclerosis by coronary computed tomography angiography influences a potential mortality benefit of statin is unknown. We evaluated the relationship between statin therapy, mortality, and subclinical atherosclerosis.MethodsIn the CONFIRM study, patients with normal or non-obstructive plaque (l50% diameter stenosis) for whom data on baseline statin use was available were included. Coronary artery calcium (CAC) was quantified using the Agatston score. The extent of non-obstructive coronary atherosclerosis was quantified using the segment involvement score (SIS). 8,016 patients were followed for a median of 2.5 years with analysis of all-cause mortality and major adverse cardiac events (MACE) including all-cause mortality, myocardial infarction, unstable angina, target vessel revascularization, and coronary artery disease-related hospitalization.Results1.2% of patients experienced all-cause mortality. Patients not on baseline statin therapy had a stepwise increased risk of all-cause mortality by CAC (relative to CAC = 0; CAC 1-99: hazard ratio [HR] 1.65, CAC 100-299: HR 2.19, and CAC≥300: HR 2.98) or SIS (relative to SIS = 0; SIS 1: HR 1.62, SIS 2-3: 2.48 and SIS≥4: 2.95). Conversely, in patients on baseline statin therapy, there was no significant increase in mortality risk with increasing CAC (p value for interaction = 0.049) or SIS (p value for interaction = 0.007). The incidence of MACE was 2.1%. Similar to the all-cause mortality, the risk of MACE was increased with CAC or SIS strata in patient not on baseline statin therapy. However, this relation was not observed in patient on baseline statin therapy.ConclusionIn individuals with non-obstructive coronary artery disease, increased risk of adverse events occurs with increasing CAC or SIS who are not on baseline statin therapy. Statin therapy is associated with a mitigation of risk of cardiac events in the presence of increasing atherosclerosis, with no particular threshold of disease burden.

Dengue-suppressing Wolbachia strains are promising tools for arbovirus control, particularly as they have the potential to self-spread following local introductions. To test this, we followed the frequency of the transinfected Wolbachia strain wMel through Ae. aegypti in Cairns, Australia, following releases at 3 nonisolated locations within the city in early 2013. Spatial spread was analysed graphically using interpolation and by fitting a statistical model describing the position and width of the wave. For the larger 2 of the 3 releases (covering 0.97 km2 and 0.52 km2), we observed slow but steady spatial spread, at about 100–200 m per year, roughly consistent with theoretical predictions. In contrast, the smallest release (0.11 km2) produced erratic temporal and spatial dynamics, with little evidence of spread after 2 years. This is consistent with the prediction concerning fitness-decreasing Wolbachia transinfections that a minimum release area is needed to achieve stable local establishment and spread in continuous habitats. Our graphical and likelihood analyses produced broadly consistent estimates of wave speed and wave width. Spread at all sites was spatially heterogeneous, suggesting that environmental heterogeneity will affect large-scale Wolbachia transformations of urban mosquito populations. The persistence and spread of Wolbachia in release areas meeting minimum area requirements indicates the promise of successful large-scale population transformation., Author summary Wolbachia are bacteria that live inside insect cells. In insects that act as viral vectors, Wolbachia can suppress virus transmission to new hosts. Wolbachia have been experimentally introduced into Aedes aegypti mosquito populations to reduce the transmission of dengue, Zika, and other arboviruses that cause human disease. Wolbachia invade populations by causing cytoplasmic incompatibility, a phenomenon whereby embryos from crosses between infected males and uninfected females fail to hatch. While Wolbachia have been shown to successfully invade and remain established in isolated Ae. aegypti populations, outward spread from urban release zones has not been previously documented. This is an important step in demonstrating that Wolbachia can be used to combat mosquito-borne infectious disease in cities. Here we describe Wolbachia spread from 2 introduction areas within Cairns in northeastern Australia at a rate of about 100–200 meters per year. Spread occurs only when introduction areas are sufficiently large. The slow rates of observed spread are broadly consistent with mathematical predictions based on estimated Ae. aegypti dispersal distances, Wolbachia dynamics, and effects seen in isolated populations. Spread is uneven and likely depends on local characteristics (e.g., barriers) that affect mosquito density and dispersal. Our data indicate that Wolbachia can be introduced locally in large cities, remain established where released, and slowly spread from release areas. These dynamics indicate that high Wolbachia infection frequencies can be established gradually across large urban areas through local releases.

Hybridization between humans and Neanderthals has resulted in a low level of Neanderthal ancestry scattered across the genomes of many modern-day humans. After hybridization, on average, selection appears to have removed Neanderthal alleles from the human population. Quantifying the strength and causes of this selection against Neanderthal ancestry is key to understanding our relationship to Neanderthals and, more broadly, how populations remain distinct after secondary contact. Here, we develop a novel method for estimating the genome-wide average strength of selection and the density of selected sites using estimates of Neanderthal allele frequency along the genomes of modern-day humans. We confirm that East Asians had somewhat higher initial levels of Neanderthal ancestry than Europeans even after accounting for selection. We find that the bulk of purifying selection against Neanderthal ancestry is best understood as acting on many weakly deleterious alleles. We propose that the majority of these alleles were effectively neutral—and segregating at high frequency—in Neanderthals, but became selected against after entering human populations of much larger effective size. While individually of small effect, these alleles potentially imposed a heavy genetic load on the early-generation human–Neanderthal hybrids. This work suggests that differences in effective population size may play a far more important role in shaping levels of introgression than previously thought., Author Summary A small percentage of Neanderthal DNA is present in the genomes of many contemporary human populations due to hybridization tens of thousands of years ago. Much of this Neanderthal DNA appears to be deleterious in humans, and natural selection is acting to remove it. One hypothesis is that the underlying alleles were not deleterious in Neanderthals, but rather represent genetic incompatibilities that became deleterious only once they were introduced to the human population. If so, reproductive barriers must have evolved rapidly between Neanderthals and humans after their split. Here, we show that observed patterns of Neanderthal ancestry in modern humans can be explained simply as a consequence of the difference in effective population size between Neanderthals and humans. Specifically, we find that on average, selection against individual Neanderthal alleles is very weak. This is consistent with the idea that Neanderthals over time accumulated many weakly deleterious alleles that in their small population were effectively neutral. However, after introgressing into larger human populations, those alleles became exposed to purifying selection. Thus, rather than being the result of hybrid incompatibilities, differences between human and Neanderthal effective population sizes appear to have played a key role in shaping our present-day shared ancestry.

All organisms live in temporally fluctuating environments. Theory predicts that the evolution of deterministic maternal effects (i.e., anticipatory maternal effects or transgenerational phenotypic plasticity) underlies adaptation to environments that fluctuate in a predictably alternating fashion over maternal-offspring generations. In contrast, randomizing maternal effects (i.e., diversifying and conservative bet-hedging), are expected to evolve in response to unpredictably fluctuating environments. Although maternal effects are common, evidence for their adaptive significance is equivocal since they can easily evolve as a correlated response to maternal selection and may or may not increase the future fitness of offspring. Using the hermaphroditic nematode Caenorhabditis elegans, we here show that the experimental evolution of maternal glycogen provisioning underlies adaptation to a fluctuating normoxia–anoxia hatching environment by increasing embryo survival under anoxia. In strictly alternating environments, we found that hermaphrodites evolved the ability to increase embryo glycogen provisioning when they experienced normoxia and to decrease embryo glycogen provisioning when they experienced anoxia. At odds with existing theory, however, populations facing irregularly fluctuating normoxia–anoxia hatching environments failed to evolve randomizing maternal effects. Instead, adaptation in these populations may have occurred through the evolution of fitness effects that percolate over multiple generations, as they maintained considerably high expected growth rates during experimental evolution despite evolving reduced fecundity and reduced embryo survival under one or two generations of anoxia. We develop theoretical models that explain why adaptation to a wide range of patterns of environmental fluctuations hinges on the existence of deterministic maternal effects, and that such deterministic maternal effects are more likely to contribute to adaptation than randomizing maternal effects., What strategies do organisms evolve to cope with an environment that varies between generations? An experimental evolution study reveals that nematode mothers evolve glycogen provisioning to protect their embryos from fluctuating oxygen levels., Author Summary Mothers can influence the phenotype of their offspring, independently of the genes that they transmit to them; such phenomena are known as “maternal effects.” Theory suggests that maternal effects can be advantageous when the environment changes between generations, but a direct demonstration of this has been missing. Using the hermaphroditic nematode Caenorhabditis elegans, we show that the experimental evolution of maternal glycogen provisioning underlies the adaptation to a fluctuating normoxia–anoxia environment by increasing the survival of embryos under anoxic conditions. Evolution of this maternal effect only occurred in populations facing oxygen deprivation during embryogenesis every other generation (i.e., where fluctuation was regular or predictable). Unexpectedly, populations facing irregularly fluctuating oxygen levels did not evolve “bet-hedging” strategies, but instead adapted by the evolution of long-term transgenerational effects. Once evolved, maternal effects can nonetheless underlie adaptation to a wide range of temporally fluctuating environments.

Despite the importance of trauma in healthspan and lifespan in humans as well as in non-human species, with one important exception the literature in both gerontology and ecology contains virtually no experimental demographic studies concerned with trauma in any species. We used dietary manipulation [full diet (F) versus sugar-only (S)] to produce four levels of frailty in 55-day old tephritid fruit flies (Anastrepha ludens) that were then subject to the trauma of cage transfer stress (n = 900/sex in each of the 4 treatments). The key results included the following: (1) there is a trauma effect caused by the transfer that depends on previous diet before transfer, new diet after transfer and gender of the fly; (2) males are more vulnerable than females; (3) if initial diet was F, flies are relatively immune against the trauma, and the subsequent diet (F or S) does not matter; (4) however if initial diet was S, then the effect of the trauma depends largely on the diet after the transfer; (5) flies transferred from S to F diets do very well in terms of remaining longevity (i.e. greatest remaining longevity), while flies transferred from S to S diet do poorly (i.e. shortest remaining longevity). We discuss both the strengths and weaknesses of this study and implications of the results.

Species distributions are known to be limited by biotic and abiotic factors at multiple temporal and spatial scales. Species distribution models, however, frequently assume a population at equilibrium in both time and space. Studies of habitat selection have repeatedly shown the difficulty of estimating resource selection if the scale or extent of analysis is incorrect. Here, we present a multi-step approach to estimate the realized and potential distribution of the endangered giant kangaroo rat. First, we estimate the potential distribution by modeling suitability at a range-wide scale using static bioclimatic variables. We then examine annual changes in extent at a population-level. We define "available" habitat based on the total suitable potential distribution at the range-wide scale. Then, within the available habitat, model changes in population extent driven by multiple measures of resource availability. By modeling distributions for a population with robust estimates of population extent through time, and ecologically relevant predictor variables, we improved the predictive ability of SDMs, as well as revealed an unanticipated relationship between population extent and precipitation at multiple scales. At a range-wide scale, the best model indicated the giant kangaroo rat was limited to areas that received little to no precipitation in the summer months. In contrast, the best model for shorter time scales showed a positive relation with resource abundance, driven by precipitation, in the current and previous year. These results suggest that the distribution of the giant kangaroo rat was limited to the wettest parts of the drier areas within the study region. This multi-step approach reinforces the differing relationship species may have with environmental variables at different scales, provides a novel method for defining "available" habitat in habitat selection studies, and suggests a way to create distribution models at spatial and temporal scales relevant to theoretical and applied ecologists.

We describe a method of identifying and counting whales using very high resolution satellite imagery through the example of southern right whales breeding in part of the Golfo Nuevo, Península Valdés in Argentina. Southern right whales have been extensively hunted over the last 300 years and although numbers have recovered from near extinction in the early 20(th) century, current populations are fragmented and are estimated at only a small fraction of pre-hunting total. Recent extreme right whale calf mortality events at Península Valdés, which constitutes the largest single population, have raised fresh concern for the future of the species. The WorldView2 satellite has a maximum 50 cm resolution and a water penetrating coastal band in the far-blue part of the spectrum that allows it to see deeper into the water column. Using an image covering 113 km², we identified 55 probable whales and 23 other features that are possibly whales, with a further 13 objects that are only detected by the coastal band. Comparison of a number of classification techniques, to automatically detect whale-like objects, showed that a simple thresholding technique of the panchromatic and coastal band delivered the best results. This is the first successful study using satellite imagery to count whales; a pragmatic, transferable method using this rapidly advancing technology that has major implications for future surveys of cetacean populations.

BackgroundThe WHO estimates that 13% of maternal mortality is due to unsafe abortion, but challenges with measurement and data quality persist. To our knowledge, no systematic assessment of the validity of studies reporting estimates of abortion-related mortality exists.Study designTo be included in this study, articles had to meet the following criteria: (1) published between September 1(st), 2000-December 1(st), 2011; (2) utilized data from a country where abortion is "considered unsafe"; (3) specified and enumerated causes of maternal death including "abortion"; (4) enumerated ≥100 maternal deaths; (5) a quantitative research study; (6) published in a peer-reviewed journal.Results7,438 articles were initially identified. Thirty-six studies were ultimately included. Overall, studies rated "Very Good" found the highest estimates of abortion related mortality (median 16%, range 1-27.4%). Studies rated "Very Poor" found the lowest overall proportion of abortion related deaths (median: 2%, range 1.3-9.4%).ConclusionsImprovements in the quality of data collection would facilitate better understanding global abortion-related mortality. Until improved data exist, better reporting of study procedures and standardization of the definition of abortion and abortion-related mortality should be encouraged.